Gastroenterology and Renal Devices Branch

1. Nocturnal Home Hemodialysis Draft Claudia C. Ruiz-Zacharek, M.D. Medical Officer / Nephrologist Gastroenterology and Renal Devices Branch

2. Overview • Background Information • Nocturnal Home Hemodialysis • Clinical Studies

3. Background Information • Conventional Hemodialysis • typically in-center, 4 hours 3 X week • Patient has a passive role during treatment • Nocturnal Home Hemodialysis • performed at home, typically at night, and while the patient sleeps. • Patient is the performer of the treatment

4. Data from the United States Renal Data System (USRDS) • Prevalence of patients on hemodialysis in the United States, 2002: 281,594 • 0.3% (843) home hemodialysis patients • 115 NHD patients in 13 centers in North America* *Lockridge, et. al., Adv Ren Replace Ther 2001; 8(4):250-256.

5. Definitions and Nomenclature • Nocturnal Hemodialysis (NHD) • Nightly Hemodialysis • Nocturnal Home Hemodialysis • In-center nocturnal hemodialysis, • Long nocturnal hemodialysis • Slow nocturnal hemodialysis, and • Daily hemodialysis.

6. Definitions and Nomenclature (cont’d) Nocturnal Home Hemodialysis • Performed at home • Absence of medical personnel • Frequency has reportedly ranged from 5-7 nights a week • Length is 6-10 hours per night

7. Definitions and Nomenclature (cont’d) Nocturnal Home Hemodialysis • Blood flows (QB) 200-300 ml/min, • Dialysate flows (QD) usually ~300 ml/min, up to 800 ml/min* * Pierratos, A. Nephrol Dial Transplant 1999; 14:2835-2840

8. Definitions and Nomenclature (cont’d) • Human factors • Physician labeling • Patient labeling • Training

9. Definitions and Nomenclature (cont’d) Human Factors • the objective is to improve human performance • reduce the burden on training and labeling • reduce the likelihood of use error and patient injury

10. Definitions and Nomenclature (cont’d) Human Factors • The objective is to improve human performance • Reduce the burden on training and labeling • Reduce the likelihood of use error and patient injury

11. Definitions and Nomenclature (cont’d) Physician’s Instructions for Use • The manual that accompanies a medical device • indications for use statement, • contraindications, • precautions and warnings.

12. Definitions and Nomenclature (cont’d) Physician’s Instructions for Use • The manual that accompanies a medical device • indications for use statement, • contraindications, • precautions and warnings. • It should also include relevant data from clinical studies and instructions for using and caring for the device.

13. Definitions and Nomenclature (cont’d) Patient Instructions for Use • The manual that accompanies a medical device • indications for use statement, • contraindications, • precautions and warnings.

14. Definitions and Nomenclature (cont’d) Patient Instructions for Use • The manual that accompanies a medical device • indications for use statement, • contraindications, • precautions and warnings. • It should also include relevant data from clinical studies and instructions for using and caring for the device.

15. Definitions and Nomenclature (cont’d) Patient Instructions for Use • The manual that accompanies a medical device • indications for use statement, • contraindications, • precautions and warnings. • It should also include relevant data from clinical studies and instructions for using and caring for the device. • Written for a person with no medical training.

16. Definitions and Nomenclature (cont’d) Training • Teaching provided by the manufacturer • Medical expert to train the lay user • Lay user to successfully use the device

17. Overview • Background Information • Nocturnal Home Hemodialysis • Clinical Studies

18. Overview • Background Information • Nocturnal Home Hemodialysis • Clinical Studies

19. Nocturnal Home Hemodialysis • Device design and Components • Human Factors Issues • Water Quality • Use of a Partner and Remote Monitoring • Vascular Access and Extracorporeal Circuit Connections • Labeling • Lay-user Training

20. Conventional Hemodialysis Patient is passive recipient Nocturnal Home Hemodialysis Patient’s active role Giver of treatment Presumably asleep troubleshooting Nocturnal Home Hemodialysis

21. Nocturnal Home Hemodialysis Considerations for device design: • Redundancy • Additional safety alarms may become necessary • Loudness • Sensitivity • Ease of understanding and correction • User friendly

22. Nocturnal Home Hemodialysis Consider the following additional safety features: • Safeguard to prevent blood access disconnections or air emboli • Type of vascular access • Alarms to detect fluid leaks • Moisture detector • Software to include remote monitoring • User-friendly instructions • Displayed screen with menus

23. Nocturnal Home Hemodialysis Human Factors Issues • User-friendly • Dispose of devices safely and effectively with minimal dangerous error • Minimal dependance on labeling and training

24. Nocturnal Home Hemodialysis Water Quality concerns • Conventional hemodialysis: 360L/week • Nocturnal Hemodialysis: 648L-1080L/week • Types of water treatment systems • Reverse osmosis (RO) • Deionization (DI) • Combination

25. Nocturnal Home Hemodialysis Water Quality concerns • Standard water quality for hemodialysis vs. higher standards • Type of water treatment system • Water source • Municipal water suppliers • Well water

26. Nocturnal Home Hemodialysis Issues on monitoring • Without a partner* • In-center hemodialysis – constant monitoring • Home hemodialysis * Raija, et.al. Experiences on Home Hemodialysis without an Assistant. Hemodialysis International 2003; 7(1):73-104.

27. Nocturnal Home Hemodialysis Issues on monitoring “Monitoring is essential for the initial 3 months of nocturnal HD therapy until the HD team is convinced the patient is stable and compliant.” * The London Daily/Nocturnal Hemodialysis Study. AJKD, 2003

28. Nocturnal Home Hemodialysis Vascular access • Arteriovenous fistula • Synthetic graft • Long-term cuffed catheter

29. Nocturnal Home Hemodialysis Vascular access • Arteriovenous fistula • Synthetic graft • Long-term cuffed catheter

30. Nocturnal Home Hemodialysis Vascular access • Arteriovenous fistula* • Synthetic graft • Long-term cuffed catheter * Quintaliani, et. al., Survival of vascular access during daily and three times a week hemodialysis. Clin Nephrol 2000; 53:372-377.

31. Nocturnal Home Hemodialysis • Vascular access location • Connection to the device • Self cannulation • Locking devices • Enuresis alarms • Moisture sensors • Single vs dual needle technique

32. Nocturnal Home Hemodialysis Labeling • Operator’s Manual • Warnings • Cautions and Precautions • Device specifications • Instructions for maintenance • Cleaning and Disinfection • Patient Labeling • Physician’s Labeling • Additional risks

33. Nocturnal Home Hemodialysis Additional risks • Inadvertent disconnections • Blood loss from increased frequency of treatments • Potential increased rate of vascular access infection • Psychological effects

34. Nocturnal Home Hemodialysis Lay user training • Conduct safe and effective NHD treatments • Length of training reported to be approx 2-8 weeks* φ *Agar, et. al., Hemodialysis International 2003; 7(4):278-289. ΦLeitch, et. al., Am J Kidney Dis 2003; 42(1):S56-60.

35. Nocturnal Home Hemodialysis Lay-user training • Appropriate use of the hemodialysis device • Interpretation and use of safety features, accessories and hemodialysis treatment itself

36. Nocturnal Home Hemodialysis Lay-user training • Water purification system • Catheter lock boxes • Moisture sensors • Monitoring device • Vascular access connection techniques • Test the adequacy of the training

37. Overview • Background Information • Nocturnal Home Hemodialysis • Clinical Studies

38. Overview • Background Information • Nocturnal Home Hemodialysis • Clinical Studies

39. Clinical Studies • Purpose • Patient selection • Study design

40. Clinical Studies Purpose To demonstrate the safety and effectiveness of the NHD devices under actual use conditions.

41. Clinical Studies FDA concerns: • Outcomes • Clearance rates • Findings • Adverse events • Training

42. Clinical Studies Reported patient selection: • Agar , et. al., Nocturnal Hemodialysis in Australia. Hemodialysis International 2003; 7(4):278-289. • Alloatti, et. al., Long Nocturnal Dialysis. Blood Purif 2002; 20:525-530. • Covic, et.al., Long-hours home haemodialysis – the best renal replacement therapy method? Q J Med 1999; 92:251-260.

43. Clinical Studies FDA concerns: • Patient selection for trial • Patient selection for marketing • Patient performs the entire treatment • Patient must wake up to attend the alarms

44. Clinical Studies Patient selection criteria: • Home environment • Water supply • Sewage • Electricity • Space • Social interaction • Patient's vascular access type and location • Availability of a partner • Patient's compliance • Psychological well being

45. Clinical Studies Study design: • Control group • Sample size • Length of follow up • Clinical endpoints • Evaluation of outcomes • Target patient population

46. Clinical Studies Other issues to be considered: • Dialysate composition and additives • Type of anticoagulation • Choice of dialyzer • Type of monitoring • Need of a partner • Vascular access • Reuse

47. Conclusion Nocturnal Home Hemodialysis Devices • Safety is a primary concern • Increased demands on patient and patient’s home/family should be assessed • Treatment may only be available to a selected population • Design of the clinical studies to demonstrate the safety and effectiveness of the device under actual use conditions should be discussed

48. References • United States Renal Data System (USRDS) www.usrds.org • Lockridge RS, Spencer M, Craft V, Pipkin M, Campbell D, McPhatter L, Albert J, Anderson H, Jennings F, and Barger T. Nocturnal Home Hemodialysis in North America. Adv Ren Replace Ther 2001; 8(4):250-256. • Pierratos, A. Nocturnal home haemodialysis: an update on a 5-year experience. Nephrol Dial Transplant 1999; 14:2835-2840 • Mehrabian S, Morgan D, Schlaeper C, Kortas C, and Lindsay RM. Equipment and water treatment considerations for the provision of quotidian home hemodialysis. Am J Kidney Dis 2003; 42:S66-S70. • Raija M, Riitta MK, Meeri K, and Eero H. Experiences on Home Hemodialysis without an Assistant. Hemodialysis International 2003; 7(1):73-104.

49. References • Heidenheim AP, Leitch R, Kortas C and Lindsay RM. Patient Monitoring in the London Daily/Nocturnal Hemodialysis Study. Am J Kidney Dis 2003; 42:S61-S65. • Quintaliani G, Buoncristiani U, Fagugli R, Kuluiranu H, Ciao G, Rondini L, Lowenthal DT, and Reboldi G. Survival of vascular access during daily and three times a week hemodialysis. Clin Nephrol 2000; 53:372-377. • Agar JWM, Somerville CA, Dwyer KM, Simmonds RE, Boddington JM, and Waldron CM. Nocturnal Hemodialysis in Australia. Hemodialysis International 2003; 7(4):278-289. • Leitch R, Ouwendyk M, Ferguson E, Clement L, Peters K, Heidenheim AP, and Lindsay RM. Nursing Issues Related to Patient Selection, Vascular Access, and Education in Quotidian Hemodialysis. Am J Kidney Dis 2003; 42(1):S56-60.

50. References • Alloatti S, Molino A, Manes M, Bonfant G, and Pellu V. Long Nocturnal Dialysis. Blood Purif 2002; 20:525-530. • Covic A, Goldsmith DJA, Venning MC, and Ackrill P. Long-hours home haemodialysis – the best renal replacement therapy method? Q J Med 1999; 92:251-260. • The following articles have not been cited in the above discussion of NHD, but may provide additional information. Copies of these may also be found in Appendix F. • Chan CT, Hanly P, Gabor J, Picton P, Pierratos A, and Floras JS. Nocturnal Hemodialysis Lowers Heart Rate during Sleep and Normalizes Its Parasympathetic and Sympathetic Modulation. Hemodialysis International 2003; 7(1):73-104.